Intratendon delivery of leukocyte-rich platelet-rich plasma at early stage promotes tendon repair in a rabbit Achilles tendinopathy model

Tendinopathy is a great obstacle in clinical practice due to its poor regenerative capacity. The influence of different stages of tendinopathy on effects of leukocyte-rich platelet-rich plasma (Lr-PRP) has not been elucidated. The aim of this study is to investigate the optimal time point for delivery of Lr-PRP on tendinopathy. A tendinopathy model was established by local collagenase injection on the rabbit Achilles tendon. Then after collagenase induction, following treatments were applied randomly on the lesion: (a) 200 mu l of Lr-PRP at 1 week (PRP-1 group), (b) 200 mu l of saline at 1 week (Saline-1 group), (c) 200 mu l of Lr-PRP at 4 weeks (PRP-2 group), and (d) 200 mu l of saline at 4 weeks (Saline-2 group). Six weeks after collagenase induction, outcomes were assessed by magnetic resonance imaging, cytokine quantification, gene expression, histology, and transmission electron microscopy. Our results demonstrated that PRP-1 group had the least cross-sectional area and lesion percent of the involved tendon, as well as the lowest signal intensity in magnetic resonance imaging among all groups. However, the PRP-2 group showed larger cross-sectional area than saline groups. Enzyme-linked immunosorbent assay indicated that PRP-1 group had a higher level of interleukin-10 but lower level of interleukin-6 when compared with PRP-2 and saline groups. Meanwhile, the highest expression of collagen (Col) 1 in PRP-1 and Col 3, matrix metalloproteinase (MMP)-1, and MMP-3 in PRP-2 was found. Histologically, the PRP-1 showed better general scores than PRP-2, and no significant difference was found between the PRP-2 and saline groups. For transmission electron microscopy, PRP-1 had the largest mean collagen fibril diameter, and the PRP-2 group showed even smaller mean collagen fibril diameter than saline groups. In conclusion, intratendon delivery of Lr-PRP at early stage showed beneficial effect for repair of tendinopathy but not at late stage. For translation of our results to clinical circumstances, further studies are still needed.